日本血吸虫虫卵外泌体Sja-miR-71a通过平衡Th17/Treg抗纤维化的作用及机制研究

外泌体（exosomes）是活细胞分泌的一种胞外囊泡，其携带miRNA参与多种疾病的发生发展，但在日本血吸虫病免疫调节和肝纤维化中的作用及机制尚不明了。最近，我们发现日本血吸虫虫卵外泌体可以抑制肝星状细胞活化，该抑制作用与其高表达的Sja-miR-71a密切相关。进一步实验显示，Sja-miR-71a能够平衡宿主Th17/Treg。由此，我们推测虫卵外泌体Sja-miR-71a通过平衡Th17/Treg，发挥抗纤维化作用，从而逃避宿主免疫攻击，确保持续感染。本项目拟采用Foxp3敲除小鼠及外泌体改造、重组腺相关病毒、Real-time PCR芯片、RNA干扰、ChIP等技术，从体内外水平探讨Sja-miR-71a平衡Th17/Treg在抗肝纤维化中的作用，并进一步明确Sja-miR-71a的靶蛋白及参与调控的信号通路，深入探讨其分子机制，为血吸虫病的治疗提供新的理论依据和治疗靶点。

Exosomes are extracellular vesicles secreted by living cells, carrying miRNAs that are involved in the occurrence and development of a variety of diseases. However, the role of immune regulation and liver fibrosis in schistosomiasis japonica are still unknown. Recently, we found that the exosomes derived from schistosoma japonicum egg can inhibit the activation of hepatic stellate cell, and this inhibition is related to the high expression of sja-miR-71a. Furthermore, sja-miR-71a can balance host Th17/Treg. Therefore, we propose that the high expression of sja-miR-71a in the exosomes of schistosoma japonicum egg play a role in anti-fibrosis by balancing Th17/Treg, leading to immune escape and persistent infection. This project will explore the role of sja-miR-71a balanced Th17/Treg in the anti-schistosomiasis liver fibrosis from in vivo and in vitro by Foxp3 knockout mice, exosomes were modified, recombinant adeno-associated virus, Real-time PCR Array, RNA interference and chromatin immunoprecipitation. Moreover, the target protein and regulated signal pathway of sja-miR-71a will clirafied to explore the molecular mechanism. This project will provide a new theoretical basis and therapeutic target for the treatment of schistosomiasis japonicum.